A quick-dissolution solid preparation is designed to achieve a rapid rise in the blood concentration of a drug administered orally in expectation of the immediate action of the drug. Therefore, in designing a quick-dissolution solid preparation, the disintegration of pharmaceutical per se, solubility and bioavailability of the drug are important considerations.
However, a drug which is sharply depressed in solubility with pH elevation is generally less efficiently absorbed in the stomach than in the intestinal tract even if it is highly disintegrable and is soluble in the gastric juice and, therefore, has the disadvantage of low bioavailability. Another disadvantage of such a drug is that it can hardly exhibit its expected efficacy in patients with achlorhydria or gastric hypoacidity.
For the purpose of enhancing the solubility of a hardly soluble drug, it is known to disperse the drug in substantially amorphous state in an inert carrier such as polyvinylpyrrolidone to thereby provide a solid solution (also known as solid dispersion) [cf. Chiou. W. L., Riegelman, S: J. Pharm. Sci., 60, 1281 (1971) and JP-A-54-2316 (the term "JP-A" as used herein means an unexamined published Japanese patent application)].
It is also known, for improving the absorption of nifedipine which is a hardly soluble drug, to coat fine beads of a water-soluble pharmaceutical additive substance with a solid solution consisting of nifedipine and polyvinylpyrrolidone (JP-A-57-85316).
It is also disclosed in JP-A-56-110612 that a preparation prepared by mixing a hardly soluble drug with a base, such as polyvinylpyrrolidone, with or without addition of a surfactant or the like, granulating the resulting composition by the fluidized-bed granulating method, and compression-molding the resulting granules is excellent in disintegration, rate of absorption, and rapidity of dissolution. In this process, anhydrous calcium hydrogenphosphate, among others, is used as the core material for fluidized-bed granulation.
However, Yakugaku Zasshi 104(5), 485-489 (1984) reports that when the hardly soluble drug nifedipine is made into a solid solution using an enteric coating base such as hydroxypropylcellulose phthalate or methacrylic acid-methyl methacrylate copolymer and coating is carried out, the rate of dissolution in JP (Japanese Pharmacopoeia) Test Solution 1 is suppressed and it is, therefore, generally acknowledged that as long as an enteric base is employed, coating with a solid solution of a hardly soluble drug may not easily provide a quick-dissolution solid preparation.